Signaling Proteins and Disease

Cells communicate through the release of specific signaling proteins that bind to their respective cell-surface receptors and transmit a signal to the cell through the receptor. These proteins are characterized by their distinct functions and the "families" of molecules to which they belong (eg, peptide hormones, growth factors, cytokines, and interleukins).

Cytokines and other signaling proteins play important roles in many critical cellular and biological processes. Though integral to these processes, their overexpression, and resulting overactivity, may also contribute to a variety of diseases. In such cases, blocking the signaling protein from binding with its receptor can yield substantial clinical benefit. However, an important challenge remains - many receptor systems are complex, requiring two or more distinct receptor components to bind signaling proteins with high affinity.

Designing Potent Inhibitors of Extracellular Signaling Proteins

Building on insights into the basic mechanisms of receptor action discovered at Regeneron, scientists have developed a general approach to create high-affinity blockers for many different types of signaling molecules. This novel Trap technology involves fusing two distinct receptor components and a portion of an antibody molecule called the "Fc" or "constant" region. The receptor domains recreate the high-affinity binding of the natural receptor for the signaling protein, while the Fc portion provides stability and improved pharmacokinetics for the novel molecule. This results in a new generation of blockers that trap the signaling molecules, preventing them from binding to the natural receptors and reducing or eliminating the harmful effects of the signaling protein.

Regeneron has successfully applied this proprietary Trap technology to create a number of therapeutic candidates such as rilonacept (IL-1 Trap), aflibercept (VEGF Trap) and the VEGF Trap-Eye.